Abstract
Abstract The transcription factor STAT5b (signal transducer and activator of transcription 5b) is implicated in tumor growth and metastases in various cancer entities including breast and prostate cancer. Activation of STAT5 signaling can be mediated via oncogene mutation (e.g. src kinase), cytokines (e.g. IL-6) and growth factors (e.g. EGF). So far, the role of STAT5b in human pancreatic adenocarcinoma (HPAC) has not been elucidated. Hence, HPAC tissue samples were investigated for nuclear STAT5b expression by immunohistochemical staining. Results show that nuclear expression of STAT5b can be detected in 42/80 HPAC tissue samples. Since specific inhibitors of STAT5b are currently not available, a shRNA approach was chosen for stable knock-down in human pancreatic cancer cells (HPAF-II, BxPC-3, L3.6pl). In vitro, no differences regarding tumor growth were detected by MTT assays and cell counts. However, knock-down of STAT5b led to significant reduction of tumor cell motility as determined in Boyden Chamber assays (P<0.05). Furthermore, upon stimulation with interleukin-6 (IL-6) and epidermal growth factor (EGF) as significant reduction in tumor cell migration was observed (P<0.05). In addition, expression of prometastatic factors Cav-1, MMP-2 and uPAR were impaired upon STAT5b blockade as determined by RT-PCR. In vivo, blockade of STAT5b significantly reduced tumor growth in subcutaneous tumor models (P<0.05). Immunohistochemical analyses of these tumors revealed no differences in tumor cell proliferation (BrdU) whereas vessel area (CD31) was significantly reduced (P<0.05). In conclusion, STAT5b is expressed in almost 50% of HPACs investigated in our study. Since blockade of STAT5b impairs tumor growth and cancer cell motility, this might be an interesting novel target for therapy of human pancreatic adenocarcinoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1658. doi:10.1158/1538-7445.AM2011-1658
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
